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1.
Braz Dent J ; 31(1): 19-24, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32159700

RESUMO

This study evaluated the association between polymorphisms in genes encoding estrogen receptors 1 (ESR1) and 2 (ESR2), vitamin D receptor (VDR) and in microRNA17 (which binds to ESR1 and VDR) with persistent apical periodontitis (PAP) after the endodontic treatment. We included 162 patients who completed endodontic treatment at least one year ago and presented apical periodontitis at the beginning of the root canal therapy. Clinical and radiographic exams were performed to evaluate the presence of PAP or healthy periradicular tissues (healed). Saliva samples were collected as a genomic DNA. The genotyping of ESR1 (rs2234693 and rs9340799), ESR2 (rs1256049 and rs4986938), VDR (rs739837 and rs2228570) and miRNA17 (rs4284505) were performed by real-time PCR. Chi-square test was used to the distribution of genotype and allele frequencies. Haplotype analysis was also performed. Eighty-nine patients were included in the "healed" group and 73 in the "PAP" group. No association was found between the allelic and genotypic polymorphisms studied and PAP (p>0.05). Haplotype analysis also did not demonstrated an association (p>0.05). In conclusion, the genetic polymorphisms in ESR1, ESR2, VDR and miRNA17 are not associated with PAP.


Assuntos
Polimorfismo Genético , Vitamina D , Estrogênios , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Polimorfismo de Nucleotídeo Único
2.
Sheng Li Xue Bao ; 72(1): 105-114, 2020 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-32099988

RESUMO

Embryo implantation is crucial for the establishment and maintenance of successful pregnancy and requires the synchronization between implantation-competent blastocyst and receptive uterus. In assisted reproductive technologies, recognition of uterine receptivity is the limiting factor for improving pregnancy rate. It has been previously reported that embryo implantation involves the activation and inactivation of numerous signaling molecules which may influence the proliferation and differentiation of uterine epithelial cells, epithelial polarity, luminal closure, embryo orientation, epithelial-stromal interactions, gland development, etc. Here we summarize the function of estrogen, progesterone, leukemia inhibitory factor (LIF), microRNA (miRNA), channel protein and signaling pathways in embryo implantation and explore their regulatory network to provide theoretical basis for the treatment of infertility and development of safe and efficient contraceptives.


Assuntos
Implantação do Embrião , Útero/fisiologia , Blastocisto/fisiologia , Estrogênios/fisiologia , Feminino , Humanos , Fator Inibidor de Leucemia/fisiologia , MicroRNAs/genética , Gravidez , Progesterona/fisiologia , Transdução de Sinais
3.
Gen Physiol Biophys ; 39(1): 27-36, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32039822

RESUMO

The G protein-coupled estrogen receptor (GPER) was proved to be a new type of estrogen receptor (ER). It is unknown that whether estrogen can regulate the secretion of gonadotrophin releasing hormone (GnRH) in GT1-7 cells through the mechanism with the involvement of GPER. The GnRH, estradiol (17ß-estradiol, E2) and GPER in peripheral blood of precocious puberty children were detected by ELISA and RT-qPCR assays. After E2 treatment, the levels of GPER and GnRH in GT1-7 cells were detected. Following G1 treatment, cell proliferation was examined using a CCK-8 assay. The levels of GnRH, KISS1, GPR54, nNOS, c-FOS in GT1-7 cells were assessed following GT1-7 cells were induced by E2 combined with G1 or G15. GnRH, E2 and GPER were significantly increased in precocious puberty children. After E2 treatment, GT1-7 cells expressed more GnRH and GPER was markedly elevated and reached a peak at 8 h. The KISS1, GPR54 and nNOS in GT1-7 cells were significantly increased with G1 induction, but were significantly decreased with G15 induction compared with E2 induction alone. Collectively, GPER cannot promote the release of GnRH via affecting the proliferation of GT1-7 cells, but it may regulate GnRH through KISS1/GPR54 pathway, which provides novel ideas for precocious puberty children treatment.


Assuntos
Puberdade Precoce , Animais , Linhagem Celular , Estradiol , Estrogênios , Hormônio Liberador de Gonadotropina , Camundongos , Receptores Estrogênicos , Receptores Acoplados a Proteínas-G
4.
J Environ Manage ; 260: 110135, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32090831

RESUMO

The occurrence of endocrine-disrupting compounds (EDCs) consisting of natural and synthetic estrogens, namely estrone (E1), 17ß-estradiol (E2), estriol (E3) and 17α-ethinylestradiol (EE2) was quantified in wastewater samples. The aim of this study was to assess the removal efficiency for the selected estrogens (E1, E2, E3 and EE2) and reduction of estrogenic activity in wastewater samples from wastewater treatment plants (WWTPs) using different processes. Solid-phase extraction (SPE) followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) methods were used to quantify the selected estrogens in wastewater samples. Estrogenic activity was assessed using the T47D-KBluc gene reporter assay. Results revealed a decrease in estrogen concentrations observed in the effluents of all the WWTPs, except for E2 at Daspoort where no removal was noted. In general, the highest removal for total estrogens was observed at Phola (84%) combining three processes (AP, BF and wetland). The AS at Daspoort had a highest removal of 75% for E3; while at Zeekoegat the highest removal reached 61% for EE2. The PST at Daspoort had no removal recorded for all the compounds, except for the EE2 (33%). The AP and BF systems at Phola contributed to a higher removal of selected compounds. Downstream of the wetland at Phola no removal was recorded for E3; while the highest removal reached 61% for E1. The best performance in terms of the overall influent-to-effluent removal efficiency was observed at Phola WWTP, where E1 removal of 85% was recorded. The highest estrogenic activity in the effluent was reported at Phola, with an average estradiol equivalent (EEQ) value of 6.3 ± 6.7 ng/L. However, no anti-estrogenic activity was detected in any of the samples. The daily mass load discharged from the effluent of the three WWTPs was higher for E1 recorded at Zeekoegat (8002.3 ± 6416.3 mg/d), followed by Daspoort (3509.8 ± 849.0 mg/d) and finally Phola (176.1 ± 34.9).


Assuntos
Águas Residuárias , Poluentes Químicos da Água , Cromatografia Líquida , Monitoramento Ambiental , Estradiol , Estrogênios , Estrona , Genes Reporter , Espectrometria de Massas em Tandem , Eliminação de Resíduos Líquidos
5.
Gene ; 736: 144406, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32007580

RESUMO

Estrogen receptor (ER) signaling is key regulator for maintaining successful pregnancy. Several research suggested that genetic variation in ER genes (ESR)1 and ESR2 is associated with the susceptibility to unexplained recurrent pregnancy loss (RPL), often with inconclusive results. In this study, we investigate the relationship between ESR1 and ESR2 polymorphisms and idiopathic RPL. A total of 444 patients with RPL, defined as three or more consecutive pregnancy losses of unknown etiology, and 446 control women were recruited to the study and their genotypes for ESR1-rs2234693, ESR1-rs3020314, and ESR2-rs928554 variants were determined using allelic exclusion method on real-time polymerase chain reaction. Minor allele frequencies (MAF) of tagging SNPs ESR1 rs2234693 and rs3020314, and ESR2 rs928554 were not significantly different between RPL cases and control women. Considerable higher frequencies of homozygous (2/2) ESR1 rs2234693 genotype carriers were seen between patients vs. control women, which maintained after controlling for age, body mass index (BMI), and menarche. ESR1 haplotype analysis demonstrated two common haplotype (rs2234693-rs3020314) with no linkage disequilibrium between both polymorphisms, and no 2-locus haplotype linked with RPL risk was revealed. The present study confirmed a significant association of specific ESR1 variant (rs2234693) with an increased risk of RPL, further supporting a role for ESR1 as an important candidate locus inducing RPL.


Assuntos
Aborto Habitual/genética , Aborto Espontâneo/genética , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Estudos de Casos e Controles , Estrogênios/genética , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Desequilíbrio de Ligação/genética , Gravidez , Estudos Retrospectivos , Tunísia
6.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(2): 220-225, 2020 Feb 15.
Artigo em Chinês | MEDLINE | ID: mdl-32030955

RESUMO

Objective: To investigate the effect of circulating estrogen level on the outcome of free fat grafting in nude mice. Methods: Eighteen female nude mice aged 6-8 weeks (weighing, 20-25 g) were randomly divided into 3 groups ( n=6). The nude mice in the ovariectomized group were treated with ovariectomy. The nude mice in the high estrogen group and the normal estrogen group only made the same incision to enter the peritoneum without ovariectomy. The nude mice in the high estrogen group were given the estradiol (0.2 mg/g) every 3 days for 30 days. The other two groups were given the same amount of PBS every 3 days. At 30 days after operation, the tail vein blood of nude mice in 3 groups were detected by estradiol ELISA kit, and the free fat (0.3 mL) donated by the females was injected into the sub-scalp of nude mice. After 8 weeks of fat grafting, the samples were taken for gross observation and weighing, and the prepared slices were stained with HE staining, CD31-perilipin fluorescence staining, immunohistochemical staining of uncoupling protein 1 (UCP1), and immunofluorescence staining of estrogen receptor α. The diameter of adipocytes and vascular density of adipose tissue were measured. The mRNA expressions of UCP1 and estrogen receptor α were detected by realtime fluorescence quantitative PCR (qRT-PCR). Results: All nude mice survived during experiment. ELISA test showed that the concentration of estradiol significantly decreased in the ovariectomized group and increased in the high estrogen group compared with the normal estrogen group ( P<0.05). At 8 weeks after fat grafting, the graft volume from large to small was ovariectomized group, normal estrogen group, and high estrogen group. There was significant difference in wet weight between the ovariectomized group and high estrogen group ( P<0.05). Section staining showed that compared with the normal estrogen group, the adipocytes in the ovariectomized group were larger, the expression of peri-lipoprotein was weaker, the vascular density decreased, and the expressions of UCP1 was negative, and the estrogen receptor α positive cells reduced. The above observation results in the high estrogen group were contrary to those in the ovariectomized group. There were significant differences in the diameter of adipocytes, the vascular density of adipose tissue, the number of the estrogen receptor α positive cells between groups ( P<0.05). The results of qRT-PCR showed that the mRNA expressions of UCP1 and estrogen receptor α significantly increased in the high estrogen group and decreased in the ovariectomized group compared with the normal estrogen group, and the differences were significant ( P<0.05). Conclusion: The level of circulating estrogen has a significant effect on the outcome of free fat grafting in nude mice. Low estrogen level leads to hypertrophy of graft adipocytes, while high estrogen level leads to the production of a large amount of beige fat and high vascular density in fat grafts, which may be related to the activation of estrogen receptor α on adipocytes.


Assuntos
Tecido Adiposo , Adipócitos , Animais , Estradiol , Estrogênios , Feminino , Camundongos , Camundongos Nus
7.
Autoimmun Rev ; 19(3): 102468, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31927086

RESUMO

In western countries, the slope of autoimmune disease (AD) incidence is increasing and affects 5-8% of the population. Mainly prevalent in women, these pathologies are due to thymic tolerance processes breakdown. The female sex hormone, estrogen, is involved in this AD female susceptibility. However, predisposition factors have to act in concert with unknown triggering environmental factors (virus, microbiota, pollution) to initiate AD. Individuals are exposed to various environmental compounds that display endocrine disruption abilities. The cellular effects of some of these molecules may be mediated through the aryl hydrocarbon receptor (AhR). Here, we review the effects of these molecules on the homeostasis of the thymic cells, the immune tolerance intrinsic factors (transcription factors, epigenetic marks) and on the immune tolerance extrinsic factors (microbiota, virus sensibility). This review highlights the contribution of estrogen and endocrine disruptors on the dysregulation of mechanisms sustaining AD development.


Assuntos
Doenças Autoimunes/imunologia , Disruptores Endócrinos/efeitos adversos , Estrogênios/imunologia , Tolerância Imunológica , Timo/efeitos dos fármacos , Feminino , Humanos , Receptores de Hidrocarboneto Arílico
8.
Sci Total Environ ; 713: 136583, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-31955091

RESUMO

Polycarbonate (PC) and polyethylene terephthalate (PET) as the package materials have been widely used for Chinese bottled water, from which estrogenic bisphenol analogues might migrate into bottled water. Therefore, there is a strong need to investigate the occurrence and potential risk of such estrogenic bisphenol analogues in Chinese bottled waters. In this study, a GC-MS method was first established and validated for determination of trace-level ten kinds of bisphenol analogues, including bisphenol A (BPA), bisphenol B (BPB), bisphenol C (BPC), bisphenol E (BPE), bisphenol F (BPF), bisphenol P (BPP), bisphenol S (BPS), bisphenol Z (BPZ), bisphenol AP (BPAP), and bisphenol AF (BPAF). BPA was detected in all eleven brands of PET bottled waters with concentrations of 12.4-44.9 ng/L. Some bisphenol analogues were detected in PET bottled waters, and the average concentrations of BPA, BPE, and BPAF in PET bottled waters were found to be 20.8, 1.8, and 2.2 ng/L, respectively. The other eight bisphenol analogues were not detected in PET bottled waters. On the other hand, BPA was detected with high concentrations of 111.8 to 6452.8 ng/L in ten brands of PC bottled water. The average concentrations of BPA, BPS, BPAP, and BPAF were determined to be 1394.3, 1.9, 1.4 and 1.0 ng/L, respectively, while the other seven bisphenol analogues were not detected. High BPA concentration detected in PC bottled waters would remarkably increase human BPA daily intake through daily consumption of such bottled waters. Meanwhile, high estrogen equivalence (EEQ) in PC bottled waters of China is mainly due to the presence of BPA, which may imply adverse effect on human. Therefore, further investigation should be dedicated to assess PC bottled water-associated BPA risks in a more holistic manner.


Assuntos
Água Potável/química , Compostos Benzidrílicos , China , Estrogênios , Fenóis
9.
Expert Rev Clin Pharmacol ; 13(2): 163-182, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31975619

RESUMO

Introduction: Steroid hormones are responsible for specific changes in the endometrium during the menstrual cycle, when they are sequentially secreted and, because of this, in the early days sequential combined oral contraceptive regimens were utilized. The same basic concept has been utilized with multi-phasic regimens, in order to produce endometrial pictures mimicking the normal cycle.Areas covered: The Endometrial effects of progestins and estrogens; combined monophasic high- (50 µg), medium- (30 µg), low- (20 µg), ultralow- (15 µg) estrogen content; sequential regimens; multiphasic combinations; treatment schedules.Cervical effects of combined high-dose and sequential combinations, including evidence for an increase in malignant lesions.Expert opinion: Overall, combined oral contraceptives (COCs) inhibit normal proliferative changes and the endometrium becomes thin, narrow, with widely spaced glands and pre-decidual changes in the stroma. During the first few cycles the progestin induces a coexistence of proliferative and secretory features; with time, the picture changes because the progestin induces a down-regulation of estrogen receptors, resulting in tortuous glands similar to those in the secretory phase, but characterized by a quiescent, atrophic glandular epithelium.In the cervical epithelium, under the influence of high-dose COCs, endocervical glands became hypersecretory and in some instances, distinctive type of atypical polypoid endocervical hyperplasia is found.


Assuntos
Anticoncepcionais Orais Combinados/administração & dosagem , Estrogênios/administração & dosagem , Progestinas/administração & dosagem , Animais , Colo do Útero/efeitos dos fármacos , Colo do Útero/metabolismo , Anticoncepcionais Orais Combinados/efeitos adversos , Anticoncepcionais Orais Combinados/farmacologia , Relação Dose-Resposta a Droga , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/metabolismo , Estrogênios/efeitos adversos , Estrogênios/farmacologia , Feminino , Humanos , Progestinas/efeitos adversos , Progestinas/farmacologia
10.
Cell Prolif ; 53(2): e12752, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31889368

RESUMO

OBJECTIVES: Insulin-like growth factor-binding protein 7 (IGFBP7) is a low-affinity insulin growth factor (IGF) binder that may play an important role in bone metabolism. We previously reported that IGFBP7 enhanced osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) via the Wnt/ß-catenin signalling pathway. In this study, we tried to reveal its function in osteoclast differentiation and osteoporosis. METHODS: We used both in vitro and in vivo studies to investigate the effects of IGFBP7 on RANKL-induced osteoclastogenesis and osteoporosis, together with the underlying molecular mechanisms of these processes. RESULTS: We show that IGFBP7 inhibited receptor activation of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis, F-actin ring formation and bone resorption, which was confirmed by using recombinant IGFBP7 protein, lentivirus and siRNA. The NF-κB signalling pathway was inhibited during this process. Moreover, in a mouse ovariectomy-induced osteoporosis model, IGFBP7 treatment attenuated osteoporotic bone loss by inhibiting osteoclast activity. CONCLUSIONS: Taken together, these findings show that IGFBP7 suppressed osteoclastogenesis in vitro and in vivo and suggest that IGFBP7 is a negative regulator of osteoclastogenesis and plays a protective role in osteoporosis. These novel insights into IGFBP7 may facilitate the development of potential treatment strategies for oestrogen deficiency-induced osteoporosis and other osteoclast-related disorders.


Assuntos
Reabsorção Óssea/metabolismo , Estrogênios/metabolismo , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Osteoclastos/metabolismo , Osteogênese/fisiologia , Ligante RANK/metabolismo , Animais , Células da Medula Óssea/metabolismo , Diferenciação Celular/fisiologia , Feminino , Masculino , Células-Tronco Mesenquimais/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Osteoblastos/metabolismo , Osteoporose/metabolismo
11.
Cell Prolif ; 53(2): e12743, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31943455

RESUMO

OBJECTIVES: Alveolar bone osteoporosis has attracted more and more attention because of its profound impact on stomatognathic function and treatment, but current treatments have not been targeted to alveolar bone and might even cause severe side effects. Thus, identifying the effects of anti-osteoporosis agents on alveolar bone is essential. Icariin ameliorates metabolic dysfunction of long bones, but its effects on alveolar bone remain unclarified. MATERIALS AND METHODS: BMSCs were isolated from rat mandibles (mBMSCs). The osteogenic potential of mBMSCs and the signalling pathway involved under icariin treatment were measured by ALP and alizarin red staining, reverse transcription-polymerase chain reaction (RT-PCR), Western blotting and immunofluorescence. Dual-luciferase assay, chromatin immunoprecipitation (ChIP) and co-immunoprecipitation were used to investigate the molecular mechanism. Ovariectomized and sham-operated rats treated with or without icariin were analysed by micro-CT, TRAP staining and calcein double labelling. RESULTS: We found that icariin promoted osteoblast differentiation of mBMSCs. Furthermore, STAT3 was critical for icariin-promoted osteoblast differentiation, as indicated by increased phosphorylation levels in icariin-treated mBMSCs, while preventing STAT3 activation blocked icariin-induced osteoblast differentiation. Mechanistically, icariin-promoted transcription of the downstream osteogenic gene osteocalcin (Ocn) through STAT3 and STAT3 bound to the promoter of Ocn. Notably, icariin prevented the alveolar bone osteoporosis induced by oestrogen deficiency through promoting bone formation. CONCLUSIONS: For the first time, our work provides evidence supporting the potential application of icariin in promoting osteogenesis and treating alveolar bone osteoporosis.


Assuntos
Perda do Osso Alveolar/tratamento farmacológico , Estrogênios/metabolismo , Flavonoides/farmacologia , Osteogênese/efeitos dos fármacos , Fator de Transcrição STAT3/metabolismo , Perda do Osso Alveolar/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Osteocalcina/efeitos dos fármacos , Osteocalcina/metabolismo , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Transdução de Sinais/efeitos dos fármacos , Transcrição Genética/efeitos dos fármacos
12.
Arch Oral Biol ; 111: 104644, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31896027

RESUMO

OBJECTIVE: This study evaluated the ability of lithium chloride (LiCl) to increase bone filling (BF) around threaded titanium implants inserted in estrogen-deficient rats and, thein-vitro effects of this drug on osteoblast-like cell viability, proliferation, mineralization and expression of bone-related markers. DESIGN: In vivo: Rats received sham surgery plus water (Estrogen-sufficient group), ovariectomy plus water (Estrogen-deficient group) or ovariectomy plus LiCl (150 mg/kg/every other day) (LiCl/estrogen-deficient group). On the 21st day after ovariectomy/sham surgeries, a threaded titanium implant was inserted in the rat tibia. BF and the number of TRAP + cells were assessed at 10, 20 and 30 days after implant placement. In vitro: Osteosarcoma SAOS-2 cells were exposed to 0, 0.01, 0.05, and 0.1 mM of LiCl; cell proliferation, viability, mineralization (alizarin red staining) and gene expressions of RUNX-2, OCN, OPN, BSP and ALP (Real Time PCR) were estimated in the cultures. RESULTS: In vivo: The estrogen-sufficient and LiCl/estrogen-deficient groups demonstrated higher percentages of BF, within the limits of implant threads, than the estrogen-deficient group at 20 and 30 days (p < 0.05). The number of TRAP + cells was lower in LiCl/estrogen-deficient than in the estrogen-deficient group at all experimental times (p < 0.05). In vitro: Cell cultures exposed to LiCl (0.01 or 0.05 mM) exhibited larger areas of mineralized matrix than the non-exposed cultures (p < 0.05) and demonstrated the highest expressions of the genes investigated. CONCLUSION: LiCl treatment improved BF around threaded titanium implants inserted in estrogen-deficient rats and stimulated matrix mineralization and overexpression of bone-formation markers in osteoblastic cells in culture.


Assuntos
Osseointegração , Animais , Densidade Óssea , Implantes Dentários , Estrogênios , Feminino , Cloreto de Lítio , Ovariectomia , Ratos , Ratos Wistar , Tíbia , Titânio
13.
Environ Monit Assess ; 192(2): 114, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31940101

RESUMO

17ß-Estradiol (E2) is a natural estrogen produced by the feminine endocrine system. It is excreted mainly through urine and feces. Exposure to E2 may affect the reproductive system of both animals and humans, especially since the removal of E2 in conventional processes and technologies present in the wastewater treatment plants is not sufficient. Chlorine is one of the most studied and used oxidant worldwide. Although there are studies that demonstrate the endocrine disrupting compounds removal like E2, its reaction with organic matter can originate by-products, namely, trihalomethanes, which are known to have high toxic potential. The main aim of the present study was to evaluate the removal of E2 (50 µg E2 L-1-maximum concentration) using peracetic acid (PAA), a seeming cleaner and innocuous alternative to chlorine. To this end, a series of jar tests were performed, using different peracetic acid concentrations (1, 5, 10, and 15 mg L-1) and contact times (10, 15, and 20 min). The results obtained showed that a peracetic acid concentration of 15 mg L-1 with a contact time of 20 min had a removal efficacy of approximately 100%. The second main goal of this study was to evaluate the ecotoxicological potential of the tested treatments on the zebrafish Danio rerio. Several oxidative stress biomarkers were evaluated, namely glutathione S-transferase, lipid peroxidation, and catalase, besides vitellogenin. Both peracetic acid and E2 caused significant increases in the oxidative stress biomarkers, although this did not lead to increased lipid peroxidation levels. In addition, peracetic acid significantly decreased the estrogenic activity of E2, as indicated by decreased vitellogenin levels. Peracetic acid demonstrated to have great potential as an alternative disinfectant for chlorine treatments, and indications for future research are discussed.


Assuntos
Monitoramento Ambiental , Estrogênios/análise , Ácido Peracético/química , Eliminação de Resíduos Líquidos/métodos , Poluentes Químicos da Água/análise , Animais , Cloro , Desinfetantes , Disruptores Endócrinos/análise , Estradiol/análise , Estrona , Humanos , Trialometanos , Vitelogeninas , Águas Residuárias
14.
N Engl J Med ; 382(4): 328-340, 2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31971678

RESUMO

BACKGROUND: Uterine fibroids are hormone-responsive neoplasms that are associated with heavy menstrual bleeding. Elagolix, an oral gonadotropin-releasing hormone antagonist resulting in rapid, reversible suppression of ovarian sex hormones, may reduce fibroid-associated bleeding. METHODS: We conducted two identical, double-blind, randomized, placebo-controlled, 6-month phase 3 trials (Elaris Uterine Fibroids 1 and 2 [UF-1 and UF-2]) to evaluate the efficacy and safety of elagolix at a dose of 300 mg twice daily with hormonal "add-back" therapy (to replace reduced levels of endogenous hormones; in this case, estradiol, 1 mg, and norethindrone acetate, 0.5 mg, once daily) in women with fibroid-associated bleeding. An elagolix-alone group was included to assess the impact of add-back therapy on the hypoestrogenic effects of elagolix. The primary end point was menstrual blood loss of less than 80 ml during the final month of treatment and at least a 50% reduction in menstrual blood loss from baseline to the final month; missing data were imputed with the use of multiple imputation. RESULTS: A total of 412 women in UF-1 and 378 women in UF-2 underwent randomization, received elagolix or placebo, and were included in the analyses. Criteria for the primary end point were met in 68.5% of 206 women in UF-1 and in 76.5% of 189 women in UF-2 who received elagolix plus add-back therapy, as compared with 8.7% of 102 women and 10% of 94 women, respectively, who received placebo (P<0.001 for both trials). Among the women who received elagolix alone, the primary end point was met in 84.1% of 104 women in UF-1 and in 77% of 95 women in UF-2. Hot flushes (in both trials) and metrorrhagia (in UF-1) occurred significantly more commonly with elagolix plus add-back therapy than with placebo. Hypoestrogenic effects of elagolix, especially decreases in bone mineral density, were attenuated with add-back therapy. CONCLUSIONS: Elagolix with add-back therapy was effective in reducing heavy menstrual bleeding in women with uterine fibroids. (Funded by AbbVie; Elaris UF-1 and Elaris UF-2 ClinicalTrials.gov numbers, NCT02654054 and NCT02691494.).


Assuntos
Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hidrocarbonetos Fluorados/uso terapêutico , Leiomioma/complicações , Menorragia/tratamento farmacológico , Pirimidinas/uso terapêutico , Adulto , Densidade Óssea/efeitos dos fármacos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Fogachos/induzido quimicamente , Humanos , Hidrocarbonetos Fluorados/efeitos adversos , Menorragia/etiologia , Pessoa de Meia-Idade , Pirimidinas/efeitos adversos , Qualidade de Vida , Índice de Gravidade de Doença , Inquéritos e Questionários
15.
Int Heart J ; 61(1): 128-137, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956144

RESUMO

Sleep and estrogen levels have an impact on neural regulation and are associated with cardiovascular (CV) events. We investigated the effects of estrogen on heart rate variability (HRV) and circadian cycle in spontaneously hypertensive rats (SHRs). Polysomnographic recording was performed in seven male and seven female SHRs during sleep. The electroencephalogram (EEG) and electromyogram (EMG) were evaluated to define active waking (AW), quiet sleep (QS), and paradoxical sleep (PS) stages. Cardiac activities were measured by RR interval of the electrocardiogram (ECG), mean arterial pressure (MAP), and power spectrum of HRV.In ECG, estrogen prolonged the RR interval in total sleep when compared with that at baseline in male SHRs (203.74 ± 6.61 versus 181.30 ± 8.06 ms, P < 0.001) and in female SHRs (169.21 ± 6.43 versus 160.76 ± 10.66 ms, P < 0.05). In HRV, the estrogen increased the high frequency (HF) in total sleep when compared with that at baseline in male SHRs (1.03 ± 0.28 versus 0.60 ± 0.43 ln (ms2), P < 0.001) and in female SHRs (0.71 ± 0.26 versus 0.42 ± 0.19 ln (ms2), P < 0.05).In male SHRs, estrogen increased the frequency of QS (26.50 ± 4.85 versus 20.79 ± 5.07, P < 0.01) and PS (25.64 ± 5.18 versus 20.14 ± 4.75, P < 0.05) stages when compared with baseline. In female SHRs, estrogen increased the percentage of delta waves in total sleep (79.87% ± 3.10% versus 76.71% ± 2.74%, P < 0.05) when compared with that at baseline.In HRV, estrogen leads to neuromodulation by increased parasympathetic tone in all SHRs, suggesting a lower risk to CV events. In sleep analyses, estrogen in male SHRs caused poor sleep quality. In contrast, estrogen in female SHRs demonstrated improved quality of sleep and decreased risk of hypertension.


Assuntos
Sistema Nervoso Autônomo/efeitos dos fármacos , Estrogênios/administração & dosagem , Sono/efeitos dos fármacos , Animais , Relógios Circadianos/efeitos dos fármacos , Eletrocardiografia , Eletroencefalografia , Estrogênios/farmacologia , Feminino , Frequência Cardíaca/efeitos dos fármacos , Masculino , Polissonografia , Ratos , Ratos Endogâmicos SHR
16.
Environ Pollut ; 256: 113384, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31677876

RESUMO

Although livestock manure, such as from swine (Sus scrofa domestica), have high capacity to introduce endocrine-disrupting free estrogens into the environment, the frequency of estrogen detections from reconnaissance studies suggest that these compounds are ubiquitous in the environment, perhaps resulting from historic manure inputs (e.g. cattle grazing residues, undocumented historic manure applications) or uncontrolled natural sources. Compared to free estrogens, conjugates of estrogens are innocuous but have greater mobility in the environment. Estrogen conjugates can also hydrolyze to re-form the potent free estrogens. The objective of this study was to identify the transport of free and conjugated estrogens to subsurface tile drains and groundwater beneath fields treated with swine manure slurry. Three field treatments were established, two receiving swine lagoon manure slurry and one with none. Manure slurry was injected into soils at a shallow depth (∼8 cm) and water samples from tile drains and shallow wells were sampled periodically for three years. Glucuronide and sulfate conjugates of 17ß-estradiol (E2) and estrone (E1) were the only estrogen compounds detected in the tile drains (total detects = 31; 5% detection frequency; conc. range = 3.9-23.1 ng L-1), indicating the important role conjugates played in the mobility of estrogens. Free estrogens and estrogen conjugates were more frequently detected in the wells compared to the tile drains (total detects = 70; 11% detection frequency; conc. range = 4.0-1.6 × 103 ng L-1). No correlations were found between estrogen compound detections and dissolved or colloidal organic carbon (OC) fractions or other water quality parameters. Estrogenic compounds were detected beneath both manure treated and non-treated plots; furthermore, the total potential estrogenic equivalents (i.e. estrogenicity of hydrolyzed conjugates + free estrogens) were similar between treated and non-treated plots.


Assuntos
Disruptores Endócrinos/análise , Estrogênios Conjugados (USP)/análise , Estrogênios/análise , Água Subterrânea/química , Esterco/análise , Águas Residuárias/química , Animais , Bioensaio , Bovinos , Estradiol/análise , Estrona/análise , Gado , Solo/química , Suínos
17.
Toxicol Lett ; 319: 22-30, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31689473

RESUMO

Cadmium (Cd) has estrogen-like activities in breast cancer; it acts as a metalloestrogen in humans. Prospective cohort studies of Cd and breast cancer risk suggest a significant relationship between increased Cd intake and cancer incidence, with more pronounced effects for estrogen receptor α (ERα)-positive breast cancers. However, a recent systematic review with the highest level of evidence demonstrated no such relationship in post-menopausal women. Thus, the reported effects of Cd in pre- and post-menopausal ERα-positive breast cancers are inconsistent. MCF-7 human breast cancer cells normally exhibit growth through estradiol-triggered ERα signaling; however, the MCF-7 cells cultured in estrogen-deprived conditions for a long time (∼ 6 months) eventually result in LTED cells that can be used to utilize to study the proliferation of ERα-positive breast cancer cells obtained from post-menopausal women. Our results showed that unlike MCF-7 cells, LTED cells showed estradiol-independent growth because of constitutively activated ERα. Moreover, Cd (∼10 nM) stimulated ERα signaling in MCF-7 cells and ERα-expressing LTED cells, but not in LTED cells; in ERα-expressing LTED cells, this effect was reversed by ICI 182,780 (an ERα antagonist). Furthermore, in comparison with MCF-7 cells, the LTED cells expressed very low levels of G protein-coupled estrogen receptor 1 (GPER1), a membrane ER capable of stimulating the estrogenic activity of Cd. These findings suggest that the estrogenic action of Cd may be suppressed in LTED cells, and potentially in post-menopausal breast cancer.


Assuntos
Cloreto de Cádmio/toxicidade , Receptor alfa de Estrogênio/metabolismo , Estrogênios/biossíntese , Estrogênios/deficiência , Receptores Estrogênicos/metabolismo , Receptores Acoplados a Proteínas-G/metabolismo , Neoplasias da Mama/metabolismo , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Feminino , Humanos , Células MCF-7
19.
Toxicol Lett ; 319: 85-94, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31730885

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is a chronic hepatic disease associated with the excessive accumulation of lipids in the liver. Premenopausal women are protected from the liver metabolic complications of obesity compared with body mass index (BMI)-matched men. This protection may be related to estrogen's ability to limit liver fat accumulation. Aryl hydrocarbon receptor (AhR), a novel regulator of NAFLD, may be an important target for regulating estrogen homeostasis. In present study, we used benzo[a]pyrene (BaP), a classic and potent ligand of AhR, to activate AhR pathway causes overexpression of the estrogen-metabolizing enzyme cytochrome P450 1A1 (CYP1A1) and affects the expression of important genes involved in hepatic lipid regulation. BaP induces CYP1A1 expression through AhR signaling and inhibits the protective effect of 17ß-estradiol (E2) on hepatic steatosis, characterized by triglyceride accumulation, and markers of liver damage are significantly elevated. The expression of adipogenic genes involved in the hepatic lipid metabolism of sterol regulatory element-binding protein-1c (SREBP-1c) was increased compared with that in the control group. Furthermore, the mRNA and protein levels of peroxisome proliferator-activated receptor alpha (PPARα), which is involved in fatty acid oxidation, were significantly reduced. Taken together, our results revealed that the steatotic effect of AhR is likely due to overexpression of the E2 metabolic enzyme CYP1A1, which affects the estrogen signaling pathway, leading to the suppression of fatty acid oxidation, inhibition of the hepatic export of triglycerides, and an increase in peripheral fat mobilization. The results from this study may help establish AhR as a novel therapeutic and preventive target for fatty liver disease.


Assuntos
Hepatopatia Gordurosa não Alcoólica/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Animais , Benzo(a)pireno/farmacologia , Citocromo P-450 CYP1A1/biossíntese , Citocromo P-450 CYP1A1/genética , Estradiol/farmacologia , Estrogênios/metabolismo , Feminino , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , PPAR alfa/biossíntese , PPAR alfa/genética , Receptores de Hidrocarboneto Arílico/agonistas , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação a Elemento Regulador de Esterol 1/biossíntese , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Triglicerídeos/metabolismo
20.
Toxicol Lett ; 319: 242-249, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733320

RESUMO

Humans are typically exposed to mixtures of substances, whereby their bioactivity can be significantly altered by co-occurring compounds. Thus, over the last years, research on combinatory effects has gained increasing attention. In particular, several xenoestrogens have been recently reported to interact synergistically, among them alternariol (AOH) and zearalenone (ZEN), two toxins produced by molds which contaminate crops or food commodities. Bisphenol A (BPA) is a potential food contaminant arising from its use in plastics and represents a well-known xenoestrogen, acting as an endocrine disruptor. However, little research was yet conducted on its impact on the bioactivity of other xenoestrogens, and vice versa. Thus, in this study, we focused on combinatory estrogenic effects of BPA with AOH and ZEN in Ishikawa cells, which represent a well-established, estrogen-sensitive human cell model. Estrogenic stimuli of the single compounds and binary combinations in constant concentration ratios were measured by assessing the activity of alkaline phosphatase, a natural reporter gene for estrogen receptor activation. In parallel, cytotoxicity was monitored by neutral red assay. For statistical analysis of combinatory effects the "combination index" model was applied. In combination with ZEN, BPA was found to cause additive estrogenic effects. Mixtures of BPA with AOH expressed moderately antagonistic to nearly additive combinatory effects, depending on the concentration ratio. Although no synergistic effects were measured in the applied chemical mixtures, additive estrogenic stimuli were observed, underlining the importance to consider the cumulative impact of endocrine active factors out of different sources and structural classes.


Assuntos
Compostos Benzidrílicos/toxicidade , Endométrio/efeitos dos fármacos , Estrogênios/toxicidade , Lactonas/toxicidade , Micotoxinas/toxicidade , Fenóis/toxicidade , Zearalenona/toxicidade , Fosfatase Alcalina/análise , Fosfatase Alcalina/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Interações de Medicamentos , Disruptores Endócrinos/toxicidade , Endométrio/citologia , Feminino , Humanos
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